Alzheimer's disease (AD) is characterized by memory loss, cognitive impairment, and behavioral changes. More than 15 million people suffer from AD worldwide and this disease is the 7th leading cause of death in the United States (1). Many neurological disorders can be attributed to deregulated protein levels in the brain. AD pathology is characterized by extra-cellular amyloid beta (Aβ) neuritic plaques and intracellular neurofibrillary tangles. Aβ plaques are toxic and progressively accumulate in the brain throughout the duration of the disease, resulting in neuronal loss and cortical atrophy. Excessive Aβ accumulation eventually involves much of the neocortex, hippocampus and many subcortical structures.
Diagnosis of AD can be performed by clinical examination using the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. This method ranges from 76 to 98% sensitivity and 61 to 84% specificity (2). The wide range partly depends on the stage of the disease at the time of examination and clinical skill. Clinical diagnosis is more accurate in later stages of the disease. Early stage AD is more difficult to diagnose. Clinical symptoms appear after significant deposition of Aβ has already occurred (3). The ability to detect early stage AD in a specific and sensitive manner prior to the occurrence of significant impairment, and the advent of new therapeutic agents that work by arresting Aβ accumulation or depletion of Aβ levels in the brain, are important to early treatment and inhibition of disease progression.
Positron Emission Tomography (PET) can measure a variety of physical parameters, including, but not limited to, absolute blood flow, glucose metabolism, and the level of a particular molecule in the brain. PET scans can also be used to distinguish patients based on diagnosis, assign risk or adverse events (e.g. suicide), or to predict treatment response. There is a need to develop PET-based methods for diagnosing and making treatment decisions in subjects having, or at risk of having a neurological disorder, such as AD. This subject matter disclosed herein addresses this need.